Kinetics of hydrochlorothiazide absorption in humans

Area of Science:

• Pharmacokinetics
• Drug Absorption
• Clinical Pharmacology

Background:

• Hydrochlorothiazide is a widely prescribed diuretic.
• Understanding its absorption kinetics is crucial for optimizing therapeutic efficacy.
• Previous studies have explored its disposition, but absorption kinetics require further elucidation.

Purpose of the Study:

• To determine the absorption kinetics of hydrochlorothiazide in adult male volunteers.
• To compare first-order versus zero-order absorption models for hydrochlorothiazide.
• To provide a detailed pharmacokinetic profile of hydrochlorothiazide absorption.

Main Methods:

• Administered a 100-mg dose of hydrochlorothiazide to four adult male volunteers.
• Monitored plasma hydrochlorothiazide levels for 48 hours post-dose.
• Utilized the pharmacokinetic computer program AUTOAN to fit data to a two-compartment open model.
• Employed the Loo-Riegelman method for additional confirmation of absorption kinetics.

Main Results:

• Zero-order absorption kinetics provided a statistically and graphically superior fit to the plasma level data compared to first-order kinetics.
• Linear plots obtained via the Loo-Riegelman method confirmed a zero-order absorption process.
• Plasma levels were monitored over a 48-hour period.

Conclusions:

• Hydrochlorothiazide absorption in humans follows zero-order kinetics.
• This finding has implications for understanding hydrochlorothiazide bioavailability and dosing strategies.
• Zero-order absorption suggests a saturable absorption process for hydrochlorothiazide.